Studying adolescent probands with serious conduct and substance problems, and their family members (192 full sib pairs, 177 families), we report a suggestive quantitative trait locus (QTL; lod score 2.7) for our empirically-derived multisubstance-dependence phenotype. We will recalculate that QTL on our full sample of almost 300 sib pairs during Yr 05. In mid-Yr 04 of the Center we separately were funded (DA-12845) for a multisite replication and extension of that QTL study. Data from adolescents and their parents now are being collected in Denver, San Diego, and Pittsburgh. Component 1 requests funds only for continuing recruitment and data-collection in Denver. DA-12845 bears the other costs. Denver will collect 300 sib pairs (nearly all with 1, many with 2, parents) by early Yr 10; probands are adolescent patients with serious substance and conduct problems. Under DA-12845 600 similar sib-pairs will be collected in San Diego and Pittsburgh. Probands and siblings complete structured interviews, yielding diagnoses and symptom counts for substance dependence and other disorders. DNA is genotyped for whole-genome scans by our Center Core C. Core B will conduct two QTL analyses for "Dependence Vulnerability" (our empirically-derived phenotype for severity of polysubstance dependence) and conduct disorder severity. Aims are: (a) To replicate our finding of a QTL for Dependence Vulnerability at the telomeric end of Chromosome 9, (b) To identify other chromosomal regions, each less than 20 centiMorgans (cM) in length, which are very likely to contain one or more genes influencing the development of early-onset dependence on drugs, including alcohol, (c) To identify several chromosomal regions which are very likely to contain one or more genes influencing the development of adolescent conduct disorder, (d) To determine whether the chromosomal regions associated with drug dependence overlap those associated with conduct disorder; this would imply that tightly-linked or identical genes underlie the frequent association of early-onset drug dependence and conduct disorder, (e) To provide adequate power for all of these analyses by participating in a multi-site collaboration, yielding a large sample carefully and consistently phenotyped by outstanding clinical researchers in adolescent substance dependence, (f) To establish, for the use of qualified researchers, a data library, which will include posted genotype and phenotype information, together with lymphoblastoid cell lines, from subjects of this research.